Antibody-Mediated Disruption of the Annexin-V Antithrombotic Shield: A New Mechanism for Thrombosis in the Antiphospholipid Syndrome

Introduction

The antiphospholipid (aPL) syndrome is a condition that manifests in patients as vascular thromboembolism or recurrent pregnancy loss together with laboratory evidence for the presence of antibodies against anionic phospholipid-protein complexes. For a recent comprehensive review, the reader is referred to Hughes et al.¹ The syndrome was first proposed to be a distinct entity, called anticardiolipin syndrome, in 1985,² and was later renamed antiphospholipid syndrome.³ The disorder was classified as “primary” in the absence of a concurrent autoimmune condition, such as systemic lupus erythematosus, or “secondary” in the presence of another such autoimmune disorder. Antiphospholipid antibodies are detected by their reactivity to anionic phospholipids (or protein-phospholipid complexes) in solid phase immunoassays, or by their inhibition of phospholipid-dependent coagulation reactions, known as the “lupus anticoagulant” effect. The ever-expanding, yet still insufficiently integrated, knowledge of this enigmatic disorder makes this area an intriguing subject for investigation.

The pathophysiologic mechanism of this syndrome has remained obscure, resulting from the apparent multiplicity of antigenic determinants recognized by the antibodies. In addition, a large number of effects¹ have been described for the antibodies in vitro and in cell culture systems. These effects, which include the paradoxical lupus anticoagulant (LAC) phenomenon, are a consequence of the numerous roles played by phospholipids in the hemostasis system and in a multitude of biologic processes. The purpose of this review is to introduce the reader to the current state of knowledge of the role of annexin-V in this disorder.

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